Drug discovery process

Natural products are a constant source of potentially active compounds for the treatment of various disorders. The Middle East and tropical regions are believed to have the richest supplies of natural products in the world. Plant derived secondary metabolites have been used by humans to treat acute infections, health disorders and chronic illness for tens of thousands of years. Only during the last 100 years have natural products been largely replaced by synthetic drugs.

The discovery of efficacious new human therapeutic agents is one of humanity’s most vital
tasks. It is an enormously demanding activity that requires creativity, a vast range of scientific
knowledge, and great persistence. It is also an exceedingly expensive activity. In an
ideal world, no education would be complete without some exposure to the ways in which
new medicines are discovered and developed. For those young people interested in science
or medicine, such knowledge is arguably mandatory....

Great efﬁciencies have been achieved in the drug discovery process as a result of technological advances in target identiﬁcation, high-throughput screening, high-throughput organic synthesis, just-in-time in vitro ADME (absorption, distribution, metabolism, and excretion), and early pharmacokinetic screening of drug leads. These advances, spanning target selection all the way through to clinical candidate selection, have placed greater and greater demands on the analytical community to develop robust high-throughput methods.

The modern drug discovery process, in general, involves the identiﬁcation of a biochemical target (usually protein target), screening of synthetic compounds or compound libraries from combinatorial chemistry/natural sources for a lead compound, and optimization of the lead compound (activity, selectivity, pharmacokinetics, etc.) for recommending a potential clinical candidate.

Despite massive efforts in drug discovery fueled by combinatory
chemistry, recombinant DNA technology, and highthroughput
screening, surprisingly few molecules make it
through the drug development process. While the reasons
are debated, it is certain that many new chemical entities
(NCEs) suffer from recurring problems that hinder development—
low water solubility, instability, or inadequate
pharmacokinetics. An estimated 43% of NCEs are poorly
water-soluble.

In a certain sense, the field of drug metabolism (DM) is standing still. More
specifically, the basic experiment of drug metabolism (i.e., administering a new
drug to an animal or human and determining the structures, amounts, and
disposition of the metabolites) has changed very little over a period of decades.
Remarkably, the experimental design and resulting data set from a typical
absorption, distribution, metabolism, and excretion (ADME) study conducted
today would be instantly recognized and understood by DM scientists from 50
years ago.

Discovery of a new chemical entity that exerts pharmacological effects for
curing or treating diseases or relieving symptoms is only the first step in
the drug developmental process. In the developmental cycle of a new
drug, the delivery of a desired amount of a therapeutic agent to the target
at a specific time or duration is as important as its discovery. In order
to realize the optimal therapeutic outcomes, a delivery system should
be designed to achieve the optimal drug concentration at a predetermined
rate and at the desired location....

In the drug discovery area, a compound with desired therapeutic properties is identiﬁed, and its structure may be modiﬁed by synthetic alterations to enhance potency and speciﬁcity or to decrease toxicity and undesired side effects. The lead drug candidate is then transitioned into the drug development area. Only small amounts of drug (typically less than a gram) are required to support the required studies in the Drug Discovery area. However larger amounts are required to support the studies conducted in the Drug Development area.

The urgent need to ensure the conservation of biological diversity is now
widely recognised, but the role of an intellectual property rights regime as
an instrument for biodiversity conservation is poorly understood and often
hotly debated. This volume is a detailed analysis of the economic and
scientific rationales for the use of a property rights-based approach to
biodiversity conservation. It discusses the justification for, and implemen-
tation of, intellectual property rights regimes as incentive systems to
encourage conservation.

Addiction is a terrible thing. It consumes and
controls us, makes us deny important truths and
blinds us to the consequences of our actions. Our
world is in the grip of a dangerous carbon habit.
Coal and oil paved the way for the developed world’s
industrial progress.

Established in 2005 by the Association of Southeast
Asian Nations (ASEAN) and with support from the
European Union (EU), the ASEAN Centre for Biodiversity)
ACB is regarded as the fi rst regional initiative to save
the ASEAN region’s critically threatened biodiversity.

The fight to stop biodiversity loss is at a
critical moment. Species are currently
going extinct at up to 1,000 times the
natural background rate. Sixty per cent of
examined ecosystem services worldwide
have been degraded.

This issue features some articles and reports
about ASEAN Heritage Parks and other
protected areas, their importance to the conservation
and sustainable use of biodiversity
resources of Southeast Asia (SEA), and the
issues and threats that need to be addressed.

Since biomarkers of safety and efficacy are becoming tools in drug development, it is
necessary to determine whether these biomarkers can qualify for applications in clinical
trials. Qualification is defined as “a conclusion that the biomarker data submitted support
use of the biomarker in drug discovery, drug development or post approval studies and
where appropriate, in regulatory decision making” (ICH E-16). A definition of validation
was proposed during the workshop.